Purpose Severe catabolism is a major problem in critical ill patients with systemic inflammatory response. In concert with other body weight regulatinghormones leptin and the recently iscovered peptides ghrelin, adiponectin and peptide YY (PYY) may be involved. The present study reports the immediate and long-term changes of these weight regulating hormones in relation to septic disease and an experimental endotoxin challenge. Material and methods Plasma concentrations of ghrelin, adiponectin, leptin and PYY in septic patients were monitored within the first 7 days after admission to a medical ICU. In an additional placebo controlled experiment 18 young healthy men were exposed either to an experimental endotoxin challenge (n=11, 4 ng lipopolysaccharide (LPS)/kg body weight) or placebo (n=7, isotonic saline) and the weight regulating hormones were determined 90 and 180 min after the injection. Results 16 consecutive patients with sepsis (mean age 67.5 yr, mean (± SEM) APACHE score 33.4±1.9) were investigated. On the day of admittance the plasma concentration of ghrelin, adiponectin, leptin and PY were elevated. Within the following 7 days ghrelin levels remained unchanged, while plasma concentrations of adiponectin, leptin and PYY further increased significantly. In experimental endotoxinemia LPS treatment decreased ghrelin and adiponectin plasma concentrations 180 min after injection. Conclusions While ghrelin was not affected by septic disease other weight regulating hormones respond to the condition with an increase and may be endocrine indicators of catabolism. This is most likely explained by the changed caloric intake during the illness and not by the septic immune response itself because the experimentally LPS-induced septic response in otherwise healthy subjects rather exhibited suppressive effects on weight regulating hormone secretion.